Glucocorticosteroids (GCS) are the most valuable drugs for relief of asthma and rhinitis. It is widely accepted that GCS exert their therapeutic efficacy by anti-inflammatory and anti-anaphylactic actions within airway and lung tissue. The long term oral use of GCS is greatly hampered by severe side effects outside the lung region. Accordingly, only a minor part of patients with asthma or rhinitis currently undergo oral GCS therapy. A better safety can be reached by delivering GCS by inhalation. However, also the potent inhaled GCS in current wide clinical use--beclomethasone 17.alpha.,21-dipropionate and budesonide--have a rather narrow safety margin and for both unwanted GCS actions within the general circulation have been reported with the highest of the recommended doses for inhalation.
Liposomes are membrane-like vesicles consisting of series of concentric lipid bilayers alternating with hydrophilic compartments. Liposomes have been used as carriers for different kinds of pharmaceutically active compounds in order to improve drug delivery and to minimize side effects of the therapy.
Glucocorticosteroids are incorporated into liposomes only at a low concentration and are poorly retained in the vesicles. Esterification of GCS in 21-position with fatty acids increases the degree of incorporation and the retention of the steroid in the vesicles. It has been shown that the fatty acid chain acts as a hydrophobic "anchor" which holds the steroid nucleus in the hydrated polar head groups of the phospholipid and thereby improves the interaction between the glucocorticosteroid and the liposome.
Liposome-encapsulated glucocorticosteroids for therapeutic use have been described (M. De Silva et al., Lancet 8130 (1979), 1320) and U.S. Pat. No. 4,693,999 describes liposomal formulations of glucocorticosteroids for inhalation.